TABLE 1

Major randomised controlled trials of antifibrotics among patients with idiopathic pulmonary fibrosis (IPF)

PhasePatientsInterventionDurationPrimary outcome(s)Key secondary outcome(s)
Nintedanib
 TOMORROW [25]II432Randomised to 1 of 4 doses nintedanib or placebo52 weeksAnnual rate of FVC decline 60 mL·year−1 in nintedanib 150 mg twice daily group versus 190 mL·year−1 in placebo groupLower incidence of AE-IPF, small decrease in SGRQ with nintedanib 150 mg twice daily
 INPULSUS I [7]III515 IPF patientsRandomised 3:2 ratio to nintedanib 150 mg twice daily or placebo52 weeksAnnual rate of decline FVC −114.7 mL nintedanib versus −239.9 mL placebo (p<0.01)No significant difference in time to first AE or proportion with AE
 INPULSIS II [7]III551 IPF patientsRandomised 3:2 ratio to nintedanib 150 mg twice daily or placebo52 weeksAnnual rate of decline FVC −113.6 mL nintedanib versus −207.3 mL placebo (p<0.01)Increase in time to first AE in nintedanib group and lower proportion with AE in nintedanib group; significant small increase in SGRQ in nintedanib group
Pirfenidone
 CAPACITY I (004) [26]III435 IPF patientsRandomised 2:1:2 pirfenidone 2403 mg·day−1, pirfenidone 1197 mg·day−1 or placebo72 weeksMean decline FVC −8% pirfenidone versus −12.4% placebo (p<0.01)Decreased proportion of patients with ≥10% decline in FVC; prolonged PFS
 CAPACITY II (006) [26]III344 IPF patientsRandomised 1:1 pirfenidone 2403 mg·day−1 or placebo72 weeksMean decline FVC −9% pirfenidone versus −9.6% placebo (p=0.5)Reduced decline in 6MWD
 ASCEND [8]III555 with IPF (surgical biopsy required if possible UIP)Randomised to pirfenidone 801 mg three times daily or placebo52 weeksProportion of patients with ≥10% decline in FVC or death reduced by 47.9% pirfenidone versus placebo (p<0.01)Decreased decline in 6MWD, improved PFS
Combination nintedanib and pirfenidone
 Safety and pharmacokinetics of nintedanib and pirfenidone in IPF [27]IIn=50: 25 patients on pirfenidone ≥3 months; 25 patients not on antifibroticNintedanib (100 mg twice daily or 150 mg twice daily) or placebo added to pirfenidone14 days (100 mg), 28 days (150 mg)Adverse events: 10 out of 21 patients on combination; 9 out of 17 patients on only nintedanibNintedanib did not affect pharmacokinetics of pirfenidone

FVC: forced vital capacity; AE: adverse event; SGRQ: St George's Respiratory Questionnaire; PFS: progression-free survival; 6MWD: 6-min walk distance; UIP: usual interstitial pneumonia.